Oral Antiviral Therapy and Monoclonal Antibody for the Treatment of COVID-19 Infection in Outpatients Receiving Anti-Cancer Treatment for Hematological Malignancies: A Multicenter Prospective Study Exploring Efficacy, Safety and Predictors of COVID-19 Lung Failure

Background: Serious complications during SARS-CoV2 infection were reported in onco-haematological patients; in addition, COVID-19 can also indirectly force the interruption or delay of cancer treatment. Early administration of oral antivirals [molnupiravir (MOL) and nirmatrelvir/ritonavir (NIR/r)] or monoclonal antibody (Sotrovimab) may reduce hospitalization and death risk. However, data in hematological patients are lacking.

Methods: Outpatients diagnosed with onco-hematologic malignancy presenting COVID-19 were treated with oral antivirals. Hospitalization and lung failure rate, overall mortality, and safety were analyzed.

Results: Overall, 83 outpatients were prospectively enrolled in the study [median (q1-q3) age of 61 (48 - 72) years; males in 52% of cases]. All subjects were affected by B.1.1.529 (omicron) SARS-CoV2 variant. Notably, 75 (90%) were fully vaccinated against SARS-CoV2.

A total of 33 (40%) was affected by HL/NHL, 21 (25%) by AML/MDS, 14 (17%) by CLL, 15 (18%) by other malignancies, including 4 ALL, 9 MM, and 2 CML.

At the time of COVID-19, 11 (13%) were hematopoietic-stem-cell transplant recipients, 19 (23%) were treated with anti-CD20, 7 (8%) were under chronic steroid therapy.

After multidisciplinary evaluation, 44 (53%) and 39 (47%) were treated with NIR/r and MOL, respectively; in addition, 14 (17%) patients underwent a combination therapy with Sotrovimab. Median (q1-q3) time from diagnosis of COVID-19 to therapy was of 1 (1-2) days. No grade 3-4 adverse events related to antiviral or Sotrovimab were reported.

Overall, 7 (8%) patients were hospitalized for COVID-19 despite therapy. By performing a univariate and multivariate logistic regression, predictors of hospitalization were: recent administration of anti-CD20 (aOR=13.03, 95%CI=1.86-91.3), chronic steroid therapy (aOR=21.37, 95%CI=1.86-244), incomplete/lack of vaccination (aOR=16.07, 95%CI=1.45-177).

Interestingly, the subgroup of patients affected by HL/NHL and CLL presented a longer viral shedding, if compared with AML/MDS and other malignancies groups (14 vs 14 vs 8 vs 8 days respectively, p=.031); similarly, persisting COVID-19 symptoms (>21 days) was significantly more frequent in HL/NHL group vs others (18% vs 0% in other groups, p=.020).

Conclusions: The early administration of oral antivirals may be safe in onco-hematologic outpatients and could reduce the risk of hospitalization and death due to SARS-COV2 infection. Nevertheless, some groups of patients are still at higher risk and need further attention.

No relevant conflicts of interest to declare.